DOSAGE Study: Upfront Dose-Reduced Chemotherapy in Older Patients with Metastatic Colorectal Cancer
DOSAGE
DOSAGE Study: a Multicenter Randomized Phase III Trial of DOSe-reduced Chemotherapy for Advanced Colorectal Cancer in Older Patients
1 other identifier
interventional
587
1 country
36
Brief Summary
The goal of this phase III, open-label, non-inferiority randomized controlled clinical trial is compare upfront dose-reduced chemotherapy with the standard dose chemotherapy in older patients ( ≥70 years) with metastasized colorectal cancer, with regard to progression-free survival (PFS). The choice between monotherapy (a fluoropyrimidine) and doublet chemotherapy (a fluoropyrimidine with oxaliplatin) will be made for each individual patient based on expected risk of chemotherapy toxicity (according to the G8 screening). Patients classified as low risk of toxicity will be randomized between doublet chemotherapy in either full-dose, or with an upfront dose-reduction of 25%. Patients classified as high risk will be randomized between monotherapy in either full-dose or upfront dose-reduction. Primary outcome is PFS. Secondary endpoints include grade ≥3 toxicity, QoL, physical functioning, overall survival, number of treatment cycles, dose reductions, hospital admissions, cumulative received dosage and cost-effectiveness.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2024
Typical duration for phase_3
36 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 6, 2024
CompletedFirst Posted
Study publicly available on registry
February 23, 2024
CompletedStudy Start
First participant enrolled
July 1, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2028
October 16, 2024
October 1, 2024
3.9 years
February 6, 2024
October 14, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-Free Survival
Time from randomization until either radiological or clinical progression or death, whichever occurs first, assessed up to at least one year.
Secondary Outcomes (12)
Quality of Life Questionnaire
At 1, 3, 6 and 12 months after randomization
Quality of Life Questionnaire
At 1, 3, 6 and 12 months after randomization
Physical functioning Questionnaire
At 1, 3, 6 and 12 months after randomization
Physical functioning Questionnaire
At 1, 3, 6 and 12 months after randomization
Grade 3-5 chemotherapy-related toxicity
Through study duration, an average of 8 months
- +7 more secondary outcomes
Study Arms (4)
Doublet therapy, full dose (low toxicity risk based on G8)
ACTIVE COMPARATORLow risk of toxicity: G8-score of 15 or higher
Doublet therapy, dose-reduced (low toxicity risk based on G8)
EXPERIMENTALLow risk of toxicity: G8-score of 15 or higher
Fluoropyrimidine monotherapy, full dose (high toxicity risk based on G8)
ACTIVE COMPARATORHigh risk of toxicity: G8-score of 14 or lower or judged as "high toxicity risk" by their treating oncologist
Fluoropyrimidine monotherapy, dose-reduced (high toxicity risk based on G8)
EXPERIMENTALHigh risk of toxicity: G8-score of 14 or lower or judged as "high toxicity risk" by their treating oncologist
Interventions
Capecitabine 1000mg / m2 oral at day 1-14 (every 3 weeks) Oxaliplatin 130mg/m2 at day 1 (every 3 weeks) OR 5-FU 400mg/m2 IV bolus at day 1 followed by 2400mg/m2 in 46 hours (every 2 weeks) Leucovorin 400mg/m2 day 1 (every 2 weeks) Oxaliplatin 85mg/m2 day 1 (every 2 weeks)
75% of: Capecitabine 1000mg / m2 oral at day 1-14 (every 3 weeks) Oxaliplatin 130mg/m2 at day 1 (every 3 weeks) OR 5-FU 400mg/m2 IV bolus at day 1 followed by 2400mg/m2 in 46 hours (every 2 weeks) Leucovorin 400mg/m2 day 1 (every 2 weeks) Oxaliplatin 85mg/m2 day 1 (every 2 weeks)
\- Capecitabine 1000mg/m2 oral at day 1-14 (every 3 weeks)
75% of: \- Capecitabine 1000mg/m2 oral at day 1-14 (every 3 weeks)
Eligibility Criteria
You may qualify if:
- Patients aged 70 years or older with colorectal cancer and distant metastases without localized treatment options.
- Patients who are candidates for first-line palliative chemotherapy as judged by their treating oncologist
- Being able to understand the Dutch language
- Adequate bone marrow and organ function: Absolute neutrophil count (ANC) \> 1.5 x 10\^9 mmol/L, Hemoglobin (Hb) \> 6.0 mmol/L, Platelets \>100 x 109 / L, Serum bilirubin ≤ 2 x upper limit of normal (ULN), serum transaminases ≤ 3 x ULN without presence of liver metastases or ≤ 5x ULN with presence of liver metastases.
You may not qualify if:
- Patients who received prior palliative chemotherapy
- Patients in whom local treatment of metastases is scheduled (i.e. liver surgery or stereotactic radiotherapy)
- Candidates for triple chemotherapy
- Patients with complete or incomplete dihydropyrimidine dehydrogenase (DPD) deficiency
- Patients with Microsatellite instable (MSI)-high colorectal cancer
- Patients with HIV or active hepatitis
- Patients with severe kidney failure (defined as GFR ≤30ml/min)
- Patients with severe cognitive deficits making informed consent not possible
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Leiden University Medical Centerlead
- Dutch Colorectal Cancer Groupcollaborator
Study Sites (36)
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, Netherlands
Noordwest Ziekenhuisgroep
Alkmaar, Netherlands
Ziekenhuis Amstelland
Amstelveen, Netherlands
Amsterdam UMC
Amsterdam, Netherlands
Rijnstate
Arnhem, Netherlands
Wilhelmina Ziekenhuis
Assen, Netherlands
Rode Kruis Ziekenhuis
Beverwijk, Netherlands
Slingeland Ziekenhuis
Doetinchem, Netherlands
Ziekenhuis Gelderse Vallei
Ede, Netherlands
Catharina Ziekenhuis
Eindhoven, Netherlands
Treant
Emmen, Netherlands
Admiraal de Ruyter Ziekenhuis
Goes, Netherlands
Beatrixziekenhuis
Gorinchem, Netherlands
Groene Hart Ziekenhuis
Gouda, Netherlands
Saxenburgh
Hardenberg, Netherlands
St. Jansdal Ziekenhuis
Harderwijk, Netherlands
Elkerliek Ziekenhuis
Helmond, Netherlands
Tergooi MC
Hilversum, Netherlands
Medisch Centrum Leeuwarden
Leeuwarden, Netherlands
Leiden University Medical Center
Leiden, Netherlands
Alrijne Ziekenhuis
Leiderdorp, Netherlands
Canisius Wilhelmina Ziekenhuis
Nijmegen, Netherlands
Laurentius Ziekenhuis
Roermond, Netherlands
Bravis ziekenhuis
Roosendaal, Netherlands
Ikazia Ziekenhuis
Rotterdam, Netherlands
Maasstad Ziekenhuis
Rotterdam, Netherlands
Ommelander Ziekenhuis
Scheemda, Netherlands
ZorgSaam Zorggroep Zeeuws-Vlaanderen
Terneuzen, Netherlands
Haaglanden Medisch Centrum
The Hague, Netherlands
Hagaziekenhuis
The Hague, Netherlands
Bernhoven
Uden, Netherlands
Diakonessenhuis
Utrecht, Netherlands
St Antonius
Utrecht, Netherlands
VieCuri Medisch Centrum
Venlo, Netherlands
Streekziekenhuis Koninging Beatrix
Winterswijk, Netherlands
Zaans Medisch Centrum
Zaandam, Netherlands
Related Publications (1)
Baltussen JC, van den Bos F, Slingerland M, Binda TRR, Liefers GJ, van den Hout WB, Fiocco M, Verschoor AJ, Cloos-van Balen M, Holterhues C, Houtsma D, Jochems A, Spierings LEAMM, van Bodegom-Vos L, Mooijaart SP, Gelderblom H, Speetjens FM, de Glas NA, Portielje JEA. DOSAGE study: protocol for a phase III non-inferiority randomised trial investigating dose-reduced chemotherapy for advanced colorectal cancer in older patients. BMJ Open. 2024 Aug 13;14(8):e089882. doi: 10.1136/bmjopen-2024-089882.
PMID: 39142680DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Johanneke Portielje, Professor
Leiden University Medical Center
- STUDY DIRECTOR
Joosje Baltussen, MD
Leiden University Medical Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor Medical Oncology
Study Record Dates
First Submitted
February 6, 2024
First Posted
February 23, 2024
Study Start
July 1, 2024
Primary Completion (Estimated)
June 1, 2028
Study Completion (Estimated)
December 1, 2028
Last Updated
October 16, 2024
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF
- Time Frame
- The datasets generated and/or analysed during the current study are not publicly available due to patient privacy but are available from the corresponding author on reasonable request
Which parts of your data(sets) will you select for publication? The datasets generated during and/or analysed during the study will not be publicly available due to participant privacy but will be available from the corresponding author on reasonable request Are there any restrictions placed on sharing/reuse of some/all of your data due to one or more of the following options? Signed informed consent Research agreement Will you publish your data open access or with restricted access? Restricted access Publishing your data (partly) with 'restricted access': what is the reason for this? Data contains privacy-sensitive information Contractual obligations Reuse by third-party through DSA. Where will you publish your (meta)data? I will not publish (meta)data outside the LUMC